KIR2DS1 and KIR2DL1-C245 Dominantly Repress NK Cell Degranulation Triggered by Monoclonal or Bispecific Antibodies, whereas Education by Uptuning Inhibitory Killer Ig-related Receptors Exerts No Advantage in Ab-dependent Cellular Cytotoxicity.

NK cell responsiveness to target cells is tuned by interactions between inhibitory NK cell receptors and their cognate HLA class I ligands in a process termed "NK cell education." Previous studies addressing the role for NK cell education in Ab-dependent cellular cytotoxicity (ADCC) show ambiguous results and do not encompass full educational resolution. In this study, we systematically characterized human NK cell CD16-triggered degranulation toward defined human tumor cell lines in the presence of either the mAb rituximab or a recently developed CD34xCD16 bispecific killer engager. Despite positive correlation between killer Ig-related receptor (KIR)-mediated education and CD16 expression, NK cells educated by one or even two inhibitory KIRs did not perform better in terms of ADCC than uneducated NK cells in either missing-self or KIR-ligand matched settings at saturating Ab concentrations. Instead, NKG2A+ NK cells consistently showed more potent ADCC in the missing-self context despite lower levels of CD16 expression. KIR2DS1+ NK cells demonstrated dampened ADCC in both the missing-self and KIR-ligand matched settings, even in the presence of its ligand HLA C2. The lower response by KIR2DS1+ NK cells was also observed when stimulated with a bispecific killer engager. Surprisingly, repression of ADCC was also observed by NKG2A+ NK cells coexpressing the inhibitory KIR2DL1-C245 receptor that confers weak education. In conclusion, our study suggests that NK cell education by inhibitory KIRs does not augment ADCC per se, whereas expression of KIR2DS1 and KIR2DL1-C245 dominantly represses ADCC. These insights add to the fundamental understanding of NK cells and may have implications for their therapeutic use.

Microbial hitchhikers on microplastics: The exchange of aquatic microbes across distinct aquatic habitats.

Microplastics (MPs) have the potential to modify aquatic microbial communities and distribute microorganisms, including pathogens. This poses a potential risk to aquatic life and human health. Despite this, the fate of 'hitchhiking' microbes on MPs that traverse different aquatic habitats remains largely unknown. To address this, we conducted a 50-day microcosm experiment, manipulating estuarine conditions to study the exchange of bacteria and microeukaryotes between river, sea and plastisphere using a long-read metabarcoding approach. Our findings revealed a significant increase in bacteria on the plastisphere, including Pseudomonas, Sphingomonas, Hyphomonas, Brevundimonas, Aquabacterium and Thalassolituus, all of which are known for their pollutant degradation capabilities, specifically polycyclic aromatic hydrocarbons. We also observed a strong association of plastic-degrading fungi (i.e., Cladosporium and Plectosphaerella) and early-diverging fungi (Cryptomycota, also known as Rozellomycota) with the plastisphere. Sea MPs were primarily colonised by fungi (70%), with a small proportion of river-transported microbes (1%-4%). The mere presence of MPs in seawater increased the relative abundance of planktonic fungi from 2% to 25%, suggesting significant exchanges between planktonic and plastisphere communities. Using microbial source tracking, we discovered that MPs only dispersed 3.5% and 5.5% of river bacterial and microeukaryotic communities into the sea, respectively. Hence, although MPs select and facilitate the dispersal of ecologically significant microorganisms, drastic compositional changes across distinct aquatic habitats are unlikely.

An unsupervised method for physical cell interaction profiling of complex tissues.

Cellular identity in complex multicellular organisms is determined in part by the physical organization of cells. However, large-scale investigation of the cellular interactome remains technically challenging. Here we develop cell interaction by multiplet sequencing (CIM-seq), an unsupervised and high-throughput method to analyze direct physical cell-cell interactions between cell types present in a tissue. CIM-seq is based on RNA sequencing of incompletely dissociated cells, followed by computational deconvolution into constituent cell types. CIM-seq estimates parameters such as number of cells and cell types in each multiplet directly from sequencing data, making it compatible with high-throughput droplet-based methods. When applied to gut epithelium or whole dissociated lung and spleen, CIM-seq correctly identifies known interactions, including those between different cell lineages and immune cells. In the colon, CIM-seq identifies a previously unrecognized goblet cell subtype expressing the wound-healing marker Plet1, which is directly adjacent to colonic stem cells. Our results demonstrate that CIM-seq is broadly applicable to unsupervised profiling of cell-type interactions in different tissue types.

Pseudomonas ability to utilize different carbon substrates and adaptation influenced by protozoan grazing.

Bacteria are major utilizers of dissolved organic matter in aquatic systems. In coastal areas bacteria are supplied with a mixture of food sources, spanning from refractory terrestrial dissolved organic matter to labile marine autochthonous organic matter. Climate scenarios indicate that in northern coastal areas, the inflow of terrestrial organic matter will increase, and autochthonous production will decrease, thus bacteria will experience a change in the food source composition. How bacteria will cope with such changes is not known. Here, we tested the ability of an isolated bacterium from the northern Baltic Sea coast, Pseudomonas sp., to adapt to varying substrates. We performed a 7-months chemostat experiment, where three different substrates were provided: glucose, representing labile autochthonous organic carbon, sodium benzoate representing refractory organic matter, and acetate - a labile but low energy food source. Growth rate has been pointed out as a key factor for fast adaptation, and since protozoan grazers speed-up the growth rate we added a ciliate to half of the incubations. The results show that the isolated Pseudomonas is adapted to utilize both labile and ring-structured refractive substrates. The growth rate was the highest on the benzoate substrate, and the production increased over time indicating that adaptation did occur. Further, our findings indicate that predation can cause Pseudomonas to change their phenotype to resist and promote survival in various carbon substrates. Genome sequencing reveals different mutations in the genome of adapted populations compared to the native populations, suggesting the adaptation of Pseudomonas sp. to changing environment.

Geochemical and Dietary Drivers of Mercury Bioaccumulation in Estuarine Benthic Invertebrates.

Sediments represent the main reservoir of mercury (Hg) in aquatic environments and may act as a source of Hg to aquatic food webs. Yet, accumulation routes of Hg from the sediment to benthic organisms are poorly constrained. We studied the bioaccumulation of inorganic and methylmercury (HgII and MeHg, respectively) from different geochemical pools of Hg into four groups of benthic invertebrates (amphipods, polychaetes, chironomids, and bivalves). The study was conducted using mesocosm experiments entailing the use of multiple isotopically enriched Hg tracers and simulation of estuarine systems with brackish water and sediment. We applied different loading regimes of nutrients and terrestrial organic matter and showed that the vertical localization and the chemical speciation of HgII and MeHg in the sediment, in combination with the diet composition of the invertebrates, consistently controlled the bioaccumulation of HgII and MeHg into the benthic organisms. Our results suggest a direct link between the concentration of MeHg in the pelagic planktonic food web and the concentration of MeHg in benthic amphipods and, to some extent, in bivalves. In contrast, the quantity of MeHg in benthic chironomids and polychaetes seems to be driven by MeHg accumulation via the benthic food web. Accounting for these geochemical and dietary drivers of Hg bioaccumulation in benthic invertebrates will be important to understand and predict Hg transfer between the benthic and the pelagic food web, under current and future environmental scenarios.

Food environment interactions after migration: a scoping review on low- and middle-income country immigrants in high-income countries.

OBJECTIVE: To map and characterise the interactions between the food environment and immigrant populations from low- and middle-income countries living in high-income countries. DESIGN: A scoping review was carried out following the framework outlined by Arksey and O'Malley, as well as Levac et al. Peer-reviewed studies in English published between 2007 and 2021 were included. Two reviewers screened and selected the papers according to predefined inclusion criteria and reporting of results follows the PRISMA-ScR guidelines. A 'Best fit' framework synthesis was carried out using the Analysis Grid for Environments Linked to Obesity (ANGELO) framework. SETTING: High-income countries. PARTICIPANTS: Immigrants from low- and middle-income countries. RESULTS: A total of sixty-eight articles were included, primarily based in the USA, as well as Canada, Australia and Europe, with immigrants originating from five regions of the globe. The analysis identified three overarching themes that interconnected different aspects of the food environment in addition to the four themes of the ANGELO framework. They demonstrate that in valuing fresh, healthy and traditional foods, immigrants were compelled to surpass barriers in order to acquire these, though children's demands, low incomes, time scarcity and mobility influenced the healthiness of the foods acquired. CONCLUSION: This study brought together evidence on interactions between immigrant populations and the food environment. Immigrants attempted to access fresh, traditional, healthier food, though they faced structural and family-level barriers that impacted the healthiness of the food they acquired. Understanding the food environment and interactions therein is key to proposing interventions and policies that can potentially impact the most vulnerable.

'Between foods and medicines': A qualitative interview study of patient experiences of the meaning and usage of oral nutritional supplements.

The aim of this study was to deepen the understanding of what oral nutritional supplements mean to patients and how this meaning connects to supplement usage, by exploring patient experiences of such supplements. Qualitative interviews were conducted in June 2019-March 2020 with ten patients with malnutrition or at nutritional risk, prescribed oral nutritional supplements by dietitians. Data were thematically analysed using systematic text condensation. Two final categories were identified: 'Oral nutritional supplements are a one-dimensional remedy' and 'Everyday oral nutritional supplement usage is regulated autonomously'. The patients described the meaning of oral nutritional supplements as nutrition. While the supplements could compensate for nutrients not eaten or be part of a helpful compensation strategy, they could not lessen the burden of altered eating. Supplement usage was described as dependent on the acceptance of taste and the priority given to nutrition in everyday life. Usage was greater when nutrients were perceived as needed, such as when striving for higher bodyweight or disease recovery. Usage was lower when a patient's own goals were not increased nutrient intake or bodyweight or when other activities were perceived as more important. Patient experiences indicated that oral nutritional supplements could serve as a remedy for malnutrition, but not for a situation of altered eating. Supplement usage was described as being regulated autonomously based on patient views on the importance of nutrition. Those views were diverse, highlighting the importance of supplement prescribers discussing treatment goals with each patient. A deeper understanding of the meaning of oral nutritional supplements and reasons for their usage from a patient perspective is crucial in order for healthcare to provide appropriate, effective nutrition therapy for malnutrition.

Terrestrial dissolved organic matter inflow drives temporal dynamics of the bacterial community of a subarctic estuary (northern Baltic Sea).

Climate change is projected to cause increased inflow of terrestrial dissolved organic matter to coastal areas in northerly regions. Estuarine bacterial community will thereby receive larger loads of organic matter and inorganic nutrients available for microbial metabolism. The composition of the bacterial community and its ecological functions may thus be affected. We studied the responses of bacterial community to inflow of terrestrial dissolved organic matter in a subarctic estuary in the northern Baltic Sea, using a 16S rRNA gene metabarcoding approach. Betaproteobacteria dominated during the spring river flush, constituting ~ 60% of the bacterial community. Bacterial diversity increased as the runoff decreased during summer, when Verrucomicrobia, Betaproteobacteria, Bacteroidetes, Gammaproteobacteria and Planctomycetes dominated the community. Network analysis revealed that a larger number of associations between bacterial populations occurred during the summer than in spring. Betaproteobacteria and Bacteroidetes populations appeared to display similar correlations to environmental factors. In spring, freshly discharged organic matter favoured specialists, while in summer a mix of autochthonous and terrestrial organic matter promoted the development of generalists. Our study indicates that increased inflows of terrestrial organic matter-loaded freshwater to coastal areas would promote specialist bacteria, which in turn might enhance the transformation of terrestrial organic matter in estuarine environments.

A qualitative exploration of dietitians' experiences of prescribing oral nutritional supplements to patients with malnutrition: A focus on shared tailoring and behaviour change support.

BACKGROUND: Oral nutritional supplements (ONS) are commonly prescribed to patients with malnutrition. Dietitians have been suggested as preferred prescribers but generally lack ONS prescribing rights. How dietitians with prescribing rights experience their professional practice of prescribing ONS remains understudied. Thus, by exploring dietitians' experiences of prescribing ONS, the present study aimed to obtain a deeper understanding of specific aspects that are of importance for dietitians when providing a nutrition therapy including ONS. METHODS: Qualitative individual interviews were conducted with 13 dietitians prescribing ONS to free-living adult outpatients with malnutrition or at nutritional risk in the hospital or primary care setting. Systematic text condensation was used for data analysis. RESULTS: Two main categories signifying important aspects were identified and labelled: 'Shared tailoring of the ONS prescription' and 'Supporting and facilitating ONS use'. First, the dietitians described tailoring the ONS prescription together with the patient, having their acceptance as a prerequisite, and being flexible regarding products and amounts prescribed. Second, they described performing different communication strategies and organising of practical issues (e.g., ONS delivery and support from others) to support and facilitate patients' ONS usage. CONCLUSIONS: The present study identifies patient involvement and the role of dietitians as behaviour change facilitators as two important aspects when dietitians prescribe ONS. These findings allow for dietitians' ideals and strategies on how to prescribe ONS to be made more visible, which can inform both clinical practice and clinical trials for future improvements in nutrition therapy to address malnutrition.

GLI1-induced mammary gland tumours are transplantable and maintain major molecular features.

Increased expression of GLI1, the main Hedgehog signalling pathway effector, is related to unfavourable prognosis and progressive disease of certain breast cancer subtypes. We used conditional transgenic mice induced to overexpress GLI1 in the mammary epithelium either alone or in combination with deletion of one Trp53 allele to address the role of elevated GLI1 expression in breast tumour initiation and progression. Induced GLI1 expression facilitates mammary gland tumour formation and this was further increased upon heterozygous deletion of Trp53. The GLI1-induced primary tumours were of different murine molecular subtypes, including Normal-likeEx , Class8Ex , Claudin-LowEx and Erbb2-likeEx . The gene expression profiles of some of the tumours correlated well with the PAM50 subtypes for human breast cancer. Whole-exome sequencing revealed somatic mutation profiles with only little overlap between the primary tumours. Orthotopically serially transplanted GLI1-induced tumours maintained the main morphological characteristics of the primary tumours for ≥10 generations. Independent of Trp53 status and molecular subtype, the serially transplanted GLI1-induced tumours were able to grow both in the absence of transgenic GLI1 expression and in the presence of the GLI1 inhibitor GANT61. These data suggest that elevated GLI1 expression has a determinant role in tumour initiation; however, additional genetic events are required for tumour progression.

Will Climate Change Influence Production and Environmental Pathways of Halogenated Natural Products?

Thousands of halogenated natural products (HNPs) pervade the terrestrial and marine environment. HNPs are generated by biotic and abiotic processes and range in complexity from low molecular mass natural halocarbons (nHCs, mostly halomethanes and haloethanes) to compounds of higher molecular mass which often contain oxygen and/or nitrogen atoms in addition to halogens (hHNPs). nHCs have a key role in regulating tropospheric and stratospheric ozone, while some hHNPs bioaccumulate and have toxic properties similar those of anthropogenic-persistent organic pollutants (POPs). Both chemical classes have common sources: biosynthesis by marine bacteria, phytoplankton, macroalgae, and some invertebrate animals, and both may be similarly impacted by alteration of production and transport pathways in a changing climate. The nHCs scientific community is advanced in investigating sources, atmospheric and oceanic transport, and forecasting climate change impacts through modeling. By contrast, these activities are nascent or nonexistent for hHNPs. The goals of this paper are to (1) review production, sources, distribution, and transport pathways of nHCs and hHNPs through water and air, pointing out areas of commonality, (2) by analogy to nHCs, argue that climate change may alter these factors for hHNPs, and (3) suggest steps to improve linkage between nHCs and hHNPs science to better understand and predict climate change impacts.

The impact of occupational and personal factors on musculoskeletal pain - a cohort study of female nurses, sonographers and teachers.

BACKGROUND: Musculoskeletal pain is common in the general population and constitutes a major public health problem. A large proportion of these conditions may be work related. The aim of this study was to explore the relative importance of physical, psychosocial and personal factors, in number of pain sites and in five specific pain sites, among women in common professions with a broad variety of occupational exposures. METHODS: A cohort of 1115 women responded to a questionnaire on ergonomic, psychosocial, personal and life-style factors, and the outcome measure of musculoskeletal pain (based on frequency and intensity of complaints at nine anatomical sites), at baseline and at follow-up. Sum scores of ergonomic and psychosocial factors were created. The importance of exposure at baseline for the number of pain sites at follow-up were estimated using ordinal regression. The importance of exposure at baseline for pain in the neck, shoulders, hands, lower back and feet at follow-up were estimated using multi-exposure Poisson regression models. RESULTS: High sum scores for ergonomic and psychosocial factors were of importance for a high number of pain sites, although the strongest risk factor was a high number of pain sites already at baseline. On the individual level, there was a large fluctuation in number of pain sites between the two time points. Eighteen percent reported persistent (or recurrent) ≥ four pain sites, while only 11 % did not report any pain at baseline or at follow-up. Among the specific pain sites, a high sum score of ergonomic factors was associated with pain in the neck, hands and feet. A high sum score of psychosocial factors was associated with neck and shoulder pain. The strongest risk factor was, however, pain at that specific anatomical site at baseline. Only a few of the personal and life-style factors were associated with pain. CONCLUSIONS: An overwhelming majority of the women in common occupations were affected by musculoskeletal pain. Both ergonomic and psychosocial factors were predictive of a high number of pain sites and of specific pain sites. These findings indicate the need for preventive measures on the individual, organizational and societal level.

A deviation too many? Healthcare professionals' knowledge and attitudes concerning patients with intellectual disability disrupting norms regarding sexual orientation and/or gender identity.

BACKGROUND: People with intellectual disability (ID) have few role models for sexual expression and behaviour, and those who identify as LGBTQ experience dual marginalization. The aim of this study is to explore knowledge and attitudes concerning patients with both ID and norm-breaking sexuality and/or gender identity among healthcare professionals in habilitation centres. METHOD: Data were collected from four focus group interviews that included 19 healthcare professionals from child and adult teams at two Swedish habilitation centres. Data were analysed using thematic analysis. RESULTS: Three themes were identified as follows: heteronormative treatment in health care, barriers for inclusion and possibilities for inclusion. CONCLUSIONS: Norm-breaking sexuality and gender identity are still relatively invisible in habilitation centres. People with ID are still predominately desexualized and perceptions regarding their sexuality are lagging behind the rest of society. Conditions that allow for more LGBTQ-affirmative practice were described by the teams that have undergone LGBTQ training.

Legitimacy of work tasks, psychosocial work environment, and time utilization among primary care staff in Sweden.

Objective: Primary care staff faces a complex work environment including a heavy administrative work load and perceive some work tasks as illegitimate. This study aimed to elucidate associations between the perceived legitimacy of work tasks, the psychosocial work environment, and the utilization of work time among Swedish primary care staff.Design and setting: The study was designed as a multicenter study involving all staff categories, i.e. registered nurses, primary care physicians, care administrators, nurse assistants and allied professionals, at eleven primary care centers in Sweden.Subjects: Participants completed the Bern Illegitimate Tasks Scale and the Copenhagen Psychosocial Questionnaire. They also recorded time spent on all work tasks, day by day during two separate weeks.Main outcome measures and results: More than a quarter (27%) of primary care physicians perceived a high proportion of unnecessary work tasks. After adjusting for profession, age and gender, the perception of having to perform unreasonable work tasks was positively associated with experiencing role conflicts and with the proportion of organization-related administration and service work tasks.Conclusion: Across all staff groups, the perception of unreasonable work tasks was more pronounced among staff with a high proportion of non-patient related administration. Also, the perception of having to perform a large amount of illegitimate work tasks affected the psychosocial work environment negatively, which might influence staffs perception of their professional roles. These results illuminate the importance of decision makers to thoroughly consider the distribution and allocation of non-patient related work tasks among staff in primary care.Key pointsWe observed an interaction between perception of having a large proportion of illegitimate work tasks and impaired psychosocial work environment. • More than a quarter of the primary care physicians perceived a high proportion of unnecessary work tasks.• Across all staff groups, performing unreasonable work tasks was associated with an experience of having role conflicts.• Across all staff groups, a perception of performing unreasonable work tasks was associated with the proportion of non-patient related administrative work tasks.

Global change-driven effects on dissolved organic matter composition: Implications for food webs of northern lakes.

Northern ecosystems are experiencing some of the most dramatic impacts of global change on Earth. Rising temperatures, hydrological intensification, changes in atmospheric acid deposition and associated acidification recovery, and changes in vegetative cover are resulting in fundamental changes in terrestrial-aquatic biogeochemical linkages. The effects of global change are readily observed in alterations in the supply of dissolved organic matter (DOM)-the messenger between terrestrial and lake ecosystems-with potentially profound effects on the structure and function of lakes. Northern terrestrial ecosystems contain substantial stores of organic matter and filter or funnel DOM, affecting the timing and magnitude of DOM delivery to surface waters. This terrestrial DOM is processed in streams, rivers, and lakes, ultimately shifting its composition, stoichiometry, and bioavailability. Here, we explore the potential consequences of these global change-driven effects for lake food webs at northern latitudes. Notably, we provide evidence that increased allochthonous DOM supply to lakes is overwhelming increased autochthonous DOM supply that potentially results from earlier ice-out and a longer growing season. Furthermore, we assess the potential implications of this shift for the nutritional quality of autotrophs in terms of their stoichiometry, fatty acid composition, toxin production, and methylmercury concentration, and therefore, contaminant transfer through the food web. We conclude that global change in northern regions leads not only to reduced primary productivity but also to nutritionally poorer lake food webs, with discernible consequences for the trophic web to fish and humans.

Time utilization and perceived psychosocial work environment among staff in Swedish primary care settings.

BACKGROUND: Over the past decades, reorganizations and structural changes in Swedish primary care have affected time utilization among health care professionals. Consequently, increases in administrative tasks have substantially reduced the time available for face-to-face consultations. This study examined how work-time was utilized and the association between work time utilization and the perceived psychosocial work environment in Swedish primary care settings. METHODS: This descriptive, multicentre, cross-sectional study was performed in 2014-2015. Data collection began with questionnaire. In the first section, respondents were asked to estimate how their workload was distributed between patients (direct and indirect patient work) and other work tasks. The questionnaire also comprised the Copenhagen Psychosocial Questionnaire, which assessed the psychosocial work environment. Next a time study was conducted where the participants reported their work-time based on three main categories: direct patient-related work, indirect patient-related work, and other work tasks. Each main category had a number of subcategories. The participants recorded the time spent (minutes) on each work task per hour, every day, for two separate weeks. Eleven primary care centres located in southeast Sweden participated. All professionals were asked to participate (n = 441), including registered nurses, primary care physicians, care administrators, nurse assistants, and allied professionals. Response rates were 75% and 79% for the questionnaires and the time study, respectively. RESULTS: All health professionals allocated between 30.9% - 37.2% of their work-time to each main category: direct patient work, indirect patient work, and other work. All professionals estimated a higher proportion of time spent in direct patient work than they reported in the time study. Physicians scored highest on the psychosocial scales of quantitative demands, stress, and role conflicts. Among allied professionals, the proportion of work-time spent on administrative tasks was associated with more role conflicts. Younger staff perceived more adverse working conditions than older staff. CONCLUSIONS: This study indicated that Swedish primary care staff spent a limited proportion of their work time directly with patients. PCPs seemed to perceive their work environment in negative terms to a greater extent than other staff members. This study showed that work task allocations influenced the perceived psychosocial work environment.

Metapopulation theory identifies biogeographical patterns among core and satellite marine bacteria scaling from tens to thousands of kilometers.

Metapopulation theory developed in terrestrial ecology provides applicable frameworks for interpreting the role of local and regional processes in shaping species distribution patterns. Yet, empirical testing of metapopulation models on microbial communities is essentially lacking. We determined regional bacterioplankton dynamics from monthly transect sampling in the Baltic Sea Proper using 16S rRNA gene sequencing. A strong positive trend was found between local relative abundance and occupancy of populations. Notably, the occupancy-frequency distributions were significantly bimodal with a satellite mode of rare endemic populations and a core mode of abundant cosmopolitan populations (e.g. Synechococcus, SAR11 and SAR86 clade members). Temporal changes in population distributions supported several theoretical frameworks. Still, bimodality was found among bacterioplankton communities across the entire Baltic Sea, and was also frequent in globally distributed datasets. Datasets spanning waters with widely different physicochemical characteristics or environmental gradients typically lacked significant bimodal patterns. When such datasets were divided into subsets with coherent environmental conditions, bimodal patterns emerged, highlighting the importance of positive feedbacks between local abundance and occupancy within specific biomes. Thus, metapopulation theory applied to microbial biogeography can provide novel insights into the mechanisms governing shifts in biodiversity resulting from natural or anthropogenically induced changes in the environment.

A conditional transgenic mouse line for targeted expression of the stem cell marker LGR5.

LGR5 is a known marker of embryonic and adult stem cells in several tissues. In a mouse model, Lgr5+ cells have shown tumour-initiating properties, while in human cancers, such as basal cell carcinoma and colon cancer, LGR5 expression levels are increased: however, the effect of increased LGR5 expression is not fully understood. To study the effects of elevated LGR5 expression levels we generated a novel tetracycline-responsive, conditional transgenic mouse line expressing human LGR5, designated TRELGR5. In this transgenic line, LGR5 expression can be induced in any tissue depending on the expression pattern of the chosen transcriptional regulator. For the current study, we used transgenic mice with a tetracycline-regulated transcriptional transactivator linked to the bovine keratin 5 promoter (K5tTA) to drive expression of LGR5 in the epidermis. As expected, expression of human LGR5 was induced in the skin of double transgenic mice (K5tTA;TRELGR5). Inducing LGR5 expression during embryogenesis and early development resulted in macroscopically and microscopically detectable phenotypic changes, including kink tail, sparse fur coat and enlarged sebaceous glands. The fur and sebaceous gland phenotypes were reversible upon discontinued expression of transgenic LGR5, but this was not observed for the kink tail phenotype. There were no apparent phenotypic changes if LGR5 expression was induced at three weeks of age. The results demonstrate that increased expression of LGR5 during embryogenesis and the neonatal period alter skin development and homeostasis.

Dietary patterns in Swedish adults; results from a national dietary survey.

Dietary patterns derived by statistical procedures is a way to identify overall dietary habits in specific populations. The aim of this study was to identify and characterise dietary patterns in Swedish adults using data from the national dietary survey Riksmaten adults 2010-11 (952 women, 788 men). Principal component analyses were used and two patterns were identified in both sexes: a healthy pattern loading positively on vegetables, fruits, fish and seafood, and vegetable oils, and negatively on refined bread and fast food, and a Swedish traditional pattern loading positively on potatoes, meat and processed meat, full-fat milk products, sweet bakery products, sweet condiments and margarine. In addition, a light-meal pattern was identified in women with positive loadings on fibre-rich bread, cheese, rice, pasta and food grain dishes, substitute products for meat and dairy products, candies and tea. The healthy pattern was positively correlated to dietary fibre (r 0·51-0·58) and n-3 (r 0·25-0·31) (all P<0·0001), and had a higher nutrient density of folate, vitamin D and Se. The Swedish traditional and the light-meal pattern were positively correlated to added sugar (r 0·20-0·25) and the Swedish traditional also to SFA (r 0·13-0·21) (all P<0·0001); both patterns were in general negatively correlated to micronutrients. Dietary pattern scores were associated with, for example, age, physical activity, education and income. In conclusion, we identified three major dietary patterns among Swedish adults. The patterns can be further used for examining the association between whole diet and health outcomes.